As the practice of receptive anal intercourse is not limited to men who have sex with men (MSM), and there is clear evidence of both receptive vaginal and anal intercourse in the same sexual act, there is a strong rationale for the development of a microbicide formulation that is suitable for both rectal and vaginal application. A dual compartment microbicide formulation will reduce the complexity of maintaining separate dosage forms for women who engage in both anal and vaginal sex. With the promising development of the IQP-0528/TFV combination vaginal gel, a novel dual vaginal and rectal gel (DuoGel) will be developed in Project 1 from the preexisting gel formulation. In addition, to directly address potential issues of user acceptability and physiological differences between the vagina and rectum in a dual chamber microbicide product, a smart suppository device will be developed that will respond to environmental changes to beideal for either vaginal or rectal delivery. The DuoGel development will comprise the formulation of a singleIQP-0528 product and the combination IQP-0528/TFV product through rheological, anti-viral, in-vitro, and exvivo toxicity and safety evaluations based on selection criteria defined by Core B (gel PK and gel spreading). Core C (microbicide efficacy and dosing), and Project 2 (API concentration from MTSA). The smart suppository will be developed to respond to the changing pH differences in the vagina and rectum through pH sensitive nanoparticles that will release pH maintaining salts to prompt ideal environment for drug delivery. Iterative evaluations between Project 1, Core B and Core C will identify a gel and suppository formulation to be moved forward in animal trials (Project 3).